Intrahepatic endothelial and Kupffer cells involved in immunosuppressive cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis.

During acute viral hepatitis, the intrahepatic tolerance sustained by immunosuppressive cytokines such as interleukin (IL)-4, IL-10, transforming growth factor (TGF)-beta and prostaglandin E2 (PGE2), produced by Kupffer cells (KC), liver sinusoidal endothelial cells (LSEC), natural killer (NK) T cells and natural regulatory T cells may be disturbed. NK cells are recruited normally in the liver and produce interferon (IFN)-gamma to control viral replication. The use of mouse hepatitis virus type 3 (MHV3) attenuated variants showing selected tropisms for KC or LSEC have allowed determining their roles in the disturbances of immune tolerance during viral hepatitis. Groups of C57BL/6 mice were infected with the pathogenic L2-MHV3 (KC+, LSEC+), low attenuated 51.6-MHV3 (KC+, LSEC-) or high attenuated CL12-MHV3 (KC-, LSEC-) variants for the first 3 days. Results showed that IL-10, TGF-beta and PGE2 production in the liver decreased in L2-MHV3-infected mice and increased in 51.6-MHV3- and CL12-MHV3-infected mice. The ratio of IFN-gamma/IL-4 in liver decreased in L2-MHV3-infected mice, while it was not (or low) altered in mice infected with the attenuated MHV3 variant mice. Phenotypic analysis of intrahepatic mononuclear cells revealed that apoptotic NK and NK T cells increased in mice infected with the L2-MHV3, but were minor in 51.6-MHV3- and CL12-MHV3-infected mice. The numbers of CD4+ forkhead box P3+ cells increased in the livers from low pathogenic CL12-MHV3 and YAC-MHV3-infected mice. These results indicate that viral permissivity of KC and LSEC is involved in the decrease of IL-10 and PGE2, while KC may play an additional role in the apoptosis of NK and NK T cells during acute viral hepatitis.

Evolución de la dosis de toxina botulínica en la espasticidad focal y la distonía cervical / Progression of botulinum toxin dosage in focal spasticity and cervical dystonia

No disponible

No disponible

Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent regulatory T-cell expansion.

Apoptotic leukocytes are endowed with immunomodulatory properties that can be used to enhance hematopoietic engraftment and prevent graft-versus-host disease (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host macrophages and not recipient dendritic cells or donor phagocytes present in the bone marrow graft as evidenced by selective cell depletion and trafficking experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta-dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on engraftment and GvHD occurrence. This highlights the role of regulatory T cells in the tolerogenic effect of apoptotic cell infusion. This novel association between apoptosis and regulatory T-cell expansion may also contribute to preventing deleterious autoimmune responses during normal turnover.

Dealing with metastatic breast cancer in elderly women: results from a French study on a large cohort carried out by the 'Observatory on Elderly Patients'.

BACKGROUND: Treatment of elderly patients with metastatic breast cancer (MBC) is not clearly defined and seems to vary according to the subjective appreciation of the physician. PATIENTS AND METHODS: After interviewing 107 French specialists qualified in oncology, data concerning 1009 MBC patients were collected: 500 patients were between 65 and 74 years and 509 were >75 years of age. Differences in diagnosis and treatment strategy were analyzed for both age groups to identify the physician's criteria of choice and the eventual use of the geriatric assessment among those criteria. RESULTS: At diagnosis, synchronous metastatic disease was more frequent in patients over 75 years old (52% versus 39%; P<0.001). Physicians indicated that treatment was based on age and on a subjective evaluation of the patient's general status. Sixty-eight per cent of younger patients and only 31% of older ones received chemotherapy (P<0.001). In the older group drug doses were lower than those usually recommended in three-quarters of cases. Only 10% of physicians considered that they under-treat patients using the FEC 50 regimen. Over 75 years of age, hormone therapy was offered to most patients, including 8% with hormone-independent tumors. Geriatric covariates were never considered. Geriatricians rarely, if ever, played a role in the therapeutic decision. CONCLUSIONS: Inclusion of elderly patients with MBC in prospective trials is warranted to define standards of care and reduce heterogeneity in the decision-making process.

Aportaciones fisiológicas de la medida continua de la saturación de oxígeno en atletas de ambos sexos que realizan pruebas de esfuerzo máximas / Physiological contributions of the continues measurement of the saturation of oxygen in athletes of both sexes during the accomplishment of an exercise stress test

El objetivo de este estudio se centra en la monitorización continua de la saturación de oxígeno en sangre en deportistas durante la realización de una prueba de esfuerzo máxima. El conocimiento de la evolución de la saturación de oxígeno durante el ejercicio podría ser un parámetro útil para la valoración de la mejora del rendimiento deportivo. La medida continua de la saturación de oxígeno en sangre mediante oximetría de pulso no necesita de un montaje de aparatos de medida tan sofisticado como los utilizados en las pruebas de esfuerzo en la actualidad. Para este trabajo se han tomado medidas durante la prueba de esfuerzo máxima en tapiz rodante y la recuperación (5 min) en una población de 51 deportistas sanos voluntarios (25 deportistas varones y 26 deportistas mujeres). Esta medida se ha realizado con dos oxímetros de pulso, uno comercial portátil de última generación (Pulsos-3i de Minolta) y otro un prototipo desarrollado en el Instituto de microelectrónica de Madrid. Los resultados obtenidos con este tipo de medidas oximétricas han presentado coeficientes de correlación elevados (r= 0,88), para ambos sexos, entre el consumo máximo de oxígeno y el tiempo de duración de la prueba y correlaciones muy elevadas entre el tiempo en aparecer el segundo umbral ventilatorio y el tiempo en que aparece el valor más bajo de saturación de oxígeno en sangre (r= 0,87). Esto es de gran interés, porque nos indica la saturación de oxígeno como un valor con potencial futuro en la ayuda a la determinación del segundo umbral ventilatorio (AU)

The objective of this study is the continuous measurement of blood oxygen saturation in athletes while performing an exercise stress test. The knowledge of the evolution of oxygen saturation during exercise could be a useful parameter for evaluating the improvement in sports performance. The continuous measurement of blood oxygen saturation by means of pulse oximetry requires less sophisticated apparatus than current measurements. The study was performed in 51 voluntary healthy athletes (25 males and 26 females). Measurements have been performed with two pulse oximeters, one commercial portable of last generation (Pulsos-3i of Minolta) and another one that is a prototype developed at the Institute of Microelectronics of Madrid, during a treadmill test and the recovery period. The results obtained with this type of measurements presented high correlation coefficients (r= 0.88) in both sexes between VO2 max and the time of duration of the test and between the time the second threshold appeared and the time in which the lowest value of saturation of oxygen in blood (r=0.87) appeared. This is of great interest because saturation of oxygen could be a value with future potential in the determination of the second ventilatory threshold (AU)